Itch, or pruritus, is an unpleasant sensation that causes the desire to scratch. Itch sensation includes both sensory and affective components, and can be induced by chemical, mechanical and psychological factors. While acute pruritus may serve as a protective mechanism, chronic pruritus represents a significant clinical problem resulting from renal insufficiency, cholestasis, Hodgkin's lymphoma, polycythemia vera, solid tumors, HIV, as well as several serious skin diseases (Twycross et al., 2003; Ikoma et al., 2006). Chronic itching disrupts normal sleep pattern and daily activity. In the US, pruritus occurs in approximately 20% of adults, in 25% of patients with jaundice, and in 50% of patients receiving renal dialysis. Atopic dermatitis, which accompanies severe itch, is the most common childhood skin disorder affecting 15-20% of children in developed countries, and 10% of children worldwide (Flohr et al., 2004). It has been estimated that children with atopic dermatitis lose an average of 1.9 hours of sleep per night, and their parents lose an average of 2.1 hours per night (Buys, 2007). Unfortunately, chronic pruritus is often resistant to treatment (e.g., anti-histamine), and thus represents one of the major problems to society (Carroll et al., 2005). The direct cost of atopic dermatitis in the United States alone has been estimated to be 1 billion dollars per year (Carroll et al., 2005). In contrast to numerous studies on chronic pain, the research on chronic pruritus remains a relatively neglected area (Ikoma et al., 2006; Paus et al., 2006).
While significant progress concerning the cellular mechanisms of itch sensation has been made over the past several years, the molecular basis underlying itch sensation in the central nervous system was heretofore unknown. The lack of understanding of the underlying mechanisms has hindered the development of effective mechanism-based anti-pruritic drugs. There is a need in the art, therefore, for a treatment of pruritus.
Itch sensation can be induced by chemical, mechanical and psychological factors. An opioid or opiate is a general term for natural or synthetic substances that bind to specific receptors (“opioid receptors”) in the central nervous system, producing an agonist action. Opioid analgesics are extremely useful in managing severe acute pain, postoperative pain and chronic pain including cancer pain. Opioids, however, are known to induce pruritus. Consequently, there is a need in the art for combinations comprising opioids that alleviate pain, but that do not induce pruritus.